Background
Methods
Retrospective cohort study
Patients
AE determination
Meta-analysis
Data sources and study selection
Data extraction and quality assessment
Statistical analysis
Results
Retrospective cohort study
Variables | Median (interquartile range) | N |
---|---|---|
Female age (years) | 29 (5) | 737 |
Male age (years) | 34 (7) | 737 |
MII oocytes (n) | 9 (8) | 737 |
Abstinence days (n) | 4 (2) | 737 |
Semen volume (mL) | 3.20 (1.5) | 737 |
Concentration (× 106/mL) | 42.00 (36) | 737 |
Motility (%) | 50.00 (12.6) | 737 |
Forward progression motility (%) | 35.10 (9.1) | 737 |
Percentage of normal morphology (%) | 4.46 (0.94) | 737 |
Infertility duration (years) | 4 (2) | 737 |
Infertile diagnoses, n (%) | ||
Male factor | 133 (18.05%) | 737 |
Female factor | 353 (47.90%) | |
Couple factors | 251 (34.05%) | |
Infertile types, n (%) | ||
Primary infertility | 476 (64.59%) | 737 |
Secondary infertility | 261 (35.41%) | |
Ovulation inducing protocols, n (%) | ||
Conventional long pituitary downregulation protocol | 35 (4.75%) | 737 |
Modified ultra-long pituitary downregulation protocol | 702 (95.25%) | |
AE levels (μIU/106 spermatozoa) | 13.78 (12.12) | 737 |
FRa (%) | 74.30 (5944/8000) | 737 |
Meta-analysis
Literature search results
First author and year | Country | Design | N | Preparation method | Storage method | AE assay method | FR cut-off value | AE cut-off value | Outcome |
---|---|---|---|---|---|---|---|---|---|
Kruger 1988 [50] | USA | Prospective cohort | 60 | No preparation | Cryopreservation | Spectrophotometry/BAEE | > 0% vs. = 0%② | ② | |
Kennedy 1989 [6] | USA | Prospective cohort | 35 | No preparation | Fresh | Spectrophotometry/BAPNA | > 0% vs. = 0%② /= 0%③ | < 25μIU/106 spermatozoa③ | ②/③ |
Tummon 1991a [7] | USA | Prospective cohort | 87 | No preparation | Fresh | Accu-Sperm Spectrophotometry/BAPNA | > 0% vs. = 0%② /= 0%③ | < 4.5③ | ②/③ |
Tummon 1991b [7] | USA | Prospective cohort | 87 | Swim up | Fresh | Accu-Sperm Spectrophotometry/BAPNA | > 0% vs. = 0%② | ② | |
Albert 1992a [4] | France | Prospective case-control | 50 | No preparation | Fresh | MAb 4D4-proacrosin | Wholea① /> 0% vs. = 0%② /= 0%③ | ≤ 50%③ | ①/②/③ |
Albert 1992b [4] | France | Prospective case-control | 50 | Swim up | Fresh | MAb 4D4-proacrosin | > 0% vs. = 0%② | ② | |
Senn 1992a [3] | Switzerland | Prospective cohort | 151 | Discontinuous gradient | Fresh | PAb-acrosin | > 0% vs. =0%② /= 0%③ | < 60%③ | ②/③ |
Senn 1992b [3] | Switzerland | Prospective cohort | 148 | Discontinuous gradient | Fresh | PAb-hyaluronidase | > 0% vs. = 0%② /= 0%③ | < 80%③ | ②/③ |
Senn 1992c [3] | Switzerland | Prospective cohort | 96 | Discontinuous gradient | Fresh | Spectrophotometry/BAPNA | = 0%③ | < 30 μIU/106 spermatozoa③ | ③ |
De Jonge 1993 [8] | USA | Prospective cohort | 21①/60② | No preparation | Fresh | Spectrophotometry/BAPNA | > 70%b① /≥ 70% vs. < 70%② | < 12.8 μIU/106 spermatozoa | ①/② |
Sharma 1993a [54] | UK | Prospective cohort | 46 | Swim up | Fresh | Spectrophotometry/BAPNA | Whole | ① | |
Sharma 1993b [54] | UK | Prospective cohort | 31 | Discontinuous gradient | Fresh | Spectrophotometry/BAPNA | Whole | ① | |
Sharma 1993c [54] | UK | Prospective cohort | 25 | α-Chymotrypsin | Fresh | Spectrophotometry /BAPNA | Whole | ① | |
Bartoov 1994 [57] | Israel | Prospective case-control | 59 | No preparation | Fresh | Spectrophotometry /BAPNA | Whole① /> 50% vs. = 0%②/= 0%③ | ≤ 54 μIU/106 spermatozoa③ | ①/②/③ |
Sofikitis 1994 [51] | USA | Prospective cohort | 41 | No preparation | Fresh | Accu-Sperm Spectrophotometry /BAPNA | > 0% vs. = 0%② | ① | |
Yang 1994a [9] | China | Prospective cohort | 95 | No preparation | Fresh | Accu-Sperm Spectrophotometry /BAPNA | Whole① /> 0% vs. = 0%② | ①/② | |
Yang 1994b [9] | China | Prospective cohort | 95 | Swim up | Fresh | Accu-Sperm Spectrophotometry /BAPNA | Whole① /> 0% vs. = 0%② | ①/② | |
Abdul-Aziz 1995 [19] | Canada | Prospective cohort | 160 | No preparation | Fresh | Hyaluronidase target with agar/hyaluronic acid mixture substrate | Whole① | ≤ 3 mm | ① |
Henkel 1995 [16] | Germany | Prospective cohort | 110 | Swim up | Fresh | Acrosin target with gelation substrate assay | whole①/ ≤ 50%③ | < 6③ | ①/③ |
Menkveld 1996 [55] | Netherlands | Prospective cohort | 33 | No preparation | Fresh | Spectrophotometry /BAPNA | whole① /≥ 50% vs. < 50%②/< 50%③ | ≤ 18 μIU/106 spermatozoa③ | ①/②/③ |
Yie 1996 [53] | Canada | Prospective cohort | 259 | Swim up | Cryopreservation | Spectrophotometry /BAPNA | > 0% vs. 0%② /= 0%③ | ≤ 15 μIU/ μgDNA③ | ②/③ |
Langlois 2005 [56] | Belgium | Prospective cohort | 107 | No preparation | Fresh | Spectrophotometry /BAPNA | whole① /≥ 50% vs. < 50%②/< 50%③ | < 25 μIU/106 spermatozoa③ | ①/②/③ |
Tavalaee 2007 [18] | Iran | Prospective cohort | 48 | Discontinuous gradient | Fresh | Acrosin target with gelation substrate assay | whole① /< 50%③ | < 60%③ | ①/③ |
First author and year | Country | Design | N | Preparation method | Assay method | FR cut-off value | AR cut-off value | Outcome |
---|---|---|---|---|---|---|---|---|
Fénichel 1991 [47] | France | Prospective cohort | 41 | Swim up | GB24 | > 0% vs. = 0% | ② | |
Takahashi 1993 [40] | Japan | Prospective cohort | 45 | Discontinuous gradient | FITC-Con A | < 50%③ | %AR ≥ 10% at 2 h or ≤ 5% at 4 h③ | ③ |
Parinaud 1993a [37] | France | Prospective cohort | 53 | Discontinuous gradient | FITC-PNA | > 0% vs. = 0%② | ② | |
Parinaud 1993b [37] | France | Prospective cohort | 53 | Discontinuous gradient | GB24 | > 0% vs. = 0%② | ② | |
Parinaud 1995 [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | F1TC-GB24 | Wholea | ① | |
Parinaud 1995 [42] | Monaco | Prospective cohort | 131 | Discontinuous gradient | FITC-GB24 | > 0% vs. = 0%② | ② | |
Krausz 1996 [39] | Italy | Prospective cohort | 59 | Swim up | FITC-PNA | ≥ 50% vs. < 50%② | ② | |
Hershlag 1997 [44] | USA | Prospective cohort | 74 | Swim up | TRITC-PSA | Whole① | ① | |
Fujino 1997 [22] | Japan | Prospective cohort | 30 | Discontinuous gradient + Swim up | Two stain (new-methylene blue and cresyl violet) Blutstan kit | Whole① | ① | |
Rufas 1998 [64] | Israel | Prospective cohort | 62 | Discontinuous gradient | FITC-PSA | > 0% vs. = 0%② | ② | |
Kawamoto 1999 [29] | Japan | Prospective cohort | 34 | Swim up | MH61 | > 0% vs. = 0%② | ② | |
Bastiaan 2003 [63] | South Africa | Prospective cohort | 30 | Swim up | FITC-PSA | > 50% vs. < 50%② | ② | |
El-Ghobashy 2003 [33] | UK | Prospective cohort | 75 | Swim up | FITC-PSA | ≥ 50% vs. < 50%② | ② | |
Wiser 2014 [36] | Israel | Prospective cohort | 40 | Not reported | FITC-PSA | ≤ 35%③ | ≤10%③ | ③ |
First author and year | Country | Design | N | Preparation method | Inducer | Assay method | FR cut-off value | AR cut-off value | Outcome |
---|---|---|---|---|---|---|---|---|---|
Fénichel 1991 [47] | France | Prospective cohort | 41 | Swim up | A23187 | GB24 | > 0% vs. = 0%② /= 0%③ | Spontaneous AR% ≥ 11.6% and/or Induced AR% < 20.6%③ | ②/③ |
Pampiglione 1993 [23] | UK | Prospective cohort | 54 | Swim up | A23187 | Triple stain | > 0% vs. = 0%② /= 0%③ | < 31.3%③ | ②/③ |
Parinaud 1993a [37] | France | Prospective cohort | 53 | Discontinuous gradient | A23187 | FITC-PNA | > 0% vs. = 0%② | ② | |
Parinaud 1993b [37] | France | Prospective cohort | 53 | Discontinuous gradient | A23187 | GB24 | > 0% vs. = 0%② | ② | |
Henkel 1993 [59] | Germany | Prospective cohort | 74 | Swim up | Low temperature | Triple stain | < 50%③ | ≤ 10%③ | ③ |
Calvo 1994 [25] | USA | Prospective cohort | 82① /232③ | No preparation | HFF | FITC-PSA | Wholea①/= 0%③ | ≤ 5%③ | ①/③ |
Yovich 1994 [26] | Australia | Prospective cohort | 52 | Swim up /Discontinuous gradient | A23187 | FITC-PSA | = 0%③ | < 10%③ | ③ |
Parinaud 1995a [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | A23187 | FITC-GB24 | Whole① /> 0% vs. = 0%② | ①/② | |
Parinaud 1995b [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | P | FITC-GB24 | Whole① /> 0% vs. = 0%② | ①/② | |
Parinaud 1995c [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | HFF | FITC-GB24 | Whole① /> 0% vs. = 0%② | ①/② | |
Parinaud 1995d [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | CAMP | FITC-GB24 | Whole① /> 0% vs. = 0%② | ①/② | |
Parinaud 1995e [41] | Monaco | Prospective cohort | 117 | Discontinuous gradient | TPA | FITC-GB24 | Whole① /> 0% vs. = 0%② | ①/② | |
Sukcharoen 1995 [38] | UK | Prospective cohort | 41 | Discontinuous gradient | A23187 | FITC-PNA | > 0% vs. < 50%② | ② | |
Parinaud 1995a [42] | Monaco | Prospective cohort | 131 | Discontinuous gradient | A23187 | FITC-GB24 | > 0% vs. = 0%② | ② | |
Parinaud 1995b [42] | Monaco | Prospective cohort | 131 | Discontinuous gradient | TPA | FITC-GB24 | > 0% vs. = 0%② | ② | |
Brandelli 1995 [27] | Argentina | Prospective cohort | 31 | Discontinuous gradient | BSA-GlcNAc/A23187 | FITC-PSA | Whole① /≥ 30% vs. < 30%② /< 30%③ | < 0.2b③ | ①/②/③ |
Krausz 1996a [39] | Italy | Prospective cohort | 53①/51② /52③ | Swim up | A23187 | FITC-PNA | Whole① /≥ 50% vs. < 50%② /= 0%③ | ≤ 10%③ | ①/②/③ |
Krausz 1996b [39] | Italy | Prospective cohort | 59① /59② /60③ | Swim up | P | FITC-PNA | Whole① /≥ 50% vs. < 50%② /= 0%③ | ≤ 7%③ | ①/②/③ |
Carver-Ward 1996 [48] | Netherlands | Prospective cohort | 129 | Discontinuous gradient | A23187 | Anti-CD46 antibody | Whole① /≤ 30% | ≤ 10%③ | ①/③ |
Benoff 1997 [43] | USA | Prospective cohort | 58 | Swim up | Mannose | RITC-PSA | Whole① /≥ 63% vs. < 63%② /< 63%③ | ≤ 0.1c③ | ①/②/③ |
Liu 1998 [28] | Australia | Prospective cohort | 109 | Discontinuous gradient | A23187 | FITC-PSA | Whole① /> 50% vs. ≤ 50%② | ①/② | |
Rufas 1998 [64] | Israel | Prospective case-control | 62 | Discontinuous gradient | HFF | FITC-PSA | > 0% vs. = 0%② | ② | |
Fukui 2000 [30] | Japan | Prospective cohort | 39 | Discontinuous gradient | P | FITC-PSA | > 0% vs. = 0%② | ② | |
Esterhuizen 2001 [31] | South Africa | Prospective cohort | 35 | Swim up | ZP | FITC-PSA | Whole① /≤ 60%③ | ≤ 15%③ | ①/③ |
Bastiaan 2003 [63] | South Africa | Prospective cohort | 30 | Swim up | ZP | FITC-PSA | > 50% vs. < 50%② /≤ 50%③ | < 8%③ | ②/③ |
Liu 2003 [32] | Australia | Prospective cohort | 65 | Swim up | ZP | FITC-PSA | Whole① /< 30%③ | ≤ 16%③ | ①/③ |
El-Ghobashy 2003 [33] | UK | Prospective cohort | 75 | Swim up | HFF | FITC-PSA | Whole① /≥ 50% vs. < 50%② | ①/② | |
Katsuki 2005 [34] | Japan | Prospective cohort | 133 | Swim up | A23187 | FITC-PSA | > 0% vs. = 0%② /= 0%③ | < 21%③ | ②/③ |
Jędrzejczak 2005 [24] | Poland | Prospective cohort | 79 | Discontinuous gradient | A23187 | Triple stain | Whole① | ① | |
Abu 2012 [35] | South Africa | Prospective cohort | 78 | Double Swim up | ZP | FITC-PSA | Whole① | ① |
Study characteristics
Data synthesis and analysis
AE assay
Subgroup | N | Rs (95% CI) | Test(s) of heterogeneity | Significance test(s) of Rs = 0 |
P
a
| ||
---|---|---|---|---|---|---|---|
I2 (%) |
P
| Z |
P
| ||||
Overall | 13 | 0.39 (0.18–0.60) | 95.7 | 0.000 | 3.70 | 0.000 | |
Two experiments excluded | 11 | 0.38 (0.27–0.48) | 67.1 | 0.001 | 7.19 | 0.000 | |
Geographic area | |||||||
Asia | 4 | 0.24 (0.05–0.42) | 66.7 | 0.029 | 2.49 | 0.013 | < 0.001 |
North America | 1 | 0.54 (0.43–0.65) | –b | – | 9.70 | 0.000 | |
Europe | 6 | 0.46 (0.37–0.54) | 0.0 | 0.798 | 11.02 | 0.000 | |
Preparation method | |||||||
No preparation | 6 | 0.42 (0.30–0.55) | 63.4 | 0.018 | 6.72 | 0.000 | 0.04 |
Swim up | 3 | 0.27 (0.01–0.53) | 80.6 | 0.006 | 2.01 | 0.044 | |
Discontinuous gradient | 2 | 0.42 (0.23–0.60) | 0.0 | 0.893 | 4.41 | 0.000 | |
AE assay method | |||||||
Fluorometry | |||||||
MAb 4D4-proacrosin | 1 | 0.49 (0.27–0.70) | – | – | 4.43 | 0.000 | < 0.001 |
Spectrophotometry | |||||||
Spectrophotometry/BAPNA | 5 | 0.44 (0.35–0.54) | 0.0 | 0.618 | 9.08 | 0.000 | |
Accu-Sperm spectrophotometry/BAPNA | 2 | 0.09 (−0.05–0.23) | 0.0 | 0.352 | 1.22 | 0.223 | |
Substrate assay | |||||||
Acrosin target with gelatine substrate assay | 2 | 0.43 (0.30–0.56) | 0.0 | 0.997 | 6.51 | 0.000 | |
Hyaluronidase target with agar/hyaluronic acid mixture substrate assay | 1 | 0.54 (0.43–0.65) | – | – | 9.70 | 0.000 |
Subgroup | N | SMD (95% CI) | Test(s) of heterogeneity | Significance test(s) of SMD = 0 |
P
a
| |||
---|---|---|---|---|---|---|---|---|
I2 (%) |
P
| Z |
P
| |||||
Overall | 16 | 0.79 (0.53–1.05) | 74.5 | 0.000 | 5.97 | 0.000 | ||
Four experiments excluded | 12 | 0.75 (0.57–0.93) | 26.5 | 0.184 | 8.19 | 0.000 | ||
Geographic areas | ||||||||
Asia | 3 | 0.50 (0.15–0.85) | 2.3 | 0.359 | 2.77 | 0.006 | 0.026 | |
North America | 7 | 0.81 (0.39–1.22) | 74.2 | 0.001 | 3.80 | 0.000 | ||
Europe | 6 | 0.92 (0.48–1.36) | 80.8 | 0.000 | 4.08 | 0.000 | ||
Storage method | ||||||||
Cryopreservation | 2 | 0.20 (−0.11–0.52) | 0.0 | 0.425 | 1.27 | 0.204 | < 0.001 | |
Fresh | 14 | 0.89 (0.63–1.15) | 69.3 | 0.000 | 6.73 | 0.000 | ||
Preparation method | ||||||||
No preparation | 10 | 0.82 (0.50–1.13) | 63.1 | 0.004 | 5.14 | 0.000 | 0.023 | |
Swim up | 4 | 0.57 (0.20–0.94) | 53.6 | 0.091 | 3.04 | 0.002 | ||
Discontinuous gradient | 2 | 1.07 (−0.10–2.25) | 95.1 | 0.000 | 1.79 | 0.074 | ||
FR cut-off value combined with AE assay method | ||||||||
≥ 70% vs. < 70% | Spectrophotometry | NC | ||||||
Spectrophotometry/BAPNA | 1 | 0.86 (0.30–1.41) | –b | – | 3.03 | 0.002 | ||
≥ 50% vs. < 50% | Spectrophotometry | |||||||
Spectrophotometry/BAPNA | 2 | 0.94 (0.18–1.71) | 72.5 | 0.056 | 2.41 | 0.016 | ||
> 50% vs. = 0% | Spectrophotometry | |||||||
Spectrophotometry/BAPNA | 1 | 0.82 (0.26–1.38) | – | – | 2.87 | 0.004 | ||
> 0% vs. = 0% | Fluorometry | |||||||
PAb-acrosin | 1 | 1.68 (1.29–2.07) | 8.45 | 0.000 | ||||
PAb-hyaluronidase | 1 | 0.48 (0.13–0.82) | 2.68 | 0.007 | ||||
MAb 4D4-proacrosin | 2 | 0.72 (0.32–1.13) | 0.0 | 0.600 | 3.50 | 0.000 | ||
Spectrophotometry | ||||||||
Spectrophotometry/BAPNA | 2 | 1.23 (−0.74–3.19) | 93.5 | 0.000 | 1.22 | 0.221 | ||
Accu-Sperm spectrophotometry/BAPNA | 5 | 0.70 (0.41–0.99) | 22.5 | 0.271 | 4.70 | 0.000 | ||
Spectrophotometry/BAEE | 1 | −0.04 (−0.72–0.64) | – | – | 0.12 | 0.908 |
Subgroup | N | SEN (95% CI) | SPE (95% CI) | PLR (95% CI) | NLR (95% CI) | DS (95% CI) | DOR (95% CI) | AUC (95% CI) |
P
a
| |
---|---|---|---|---|---|---|---|---|---|---|
Overall | 12 | 0.57 (0.41–0.71) | 0.85 (0.73–0.93) | 3.91 (2.31–6.61) | 0.50 (0.37–0.68) | 2.05 (1.43–2.67) | 7.78 (4.19–14.46) | 0.78 (0.74–0.81) | ||
Outlier excluded | 11 | 0.51 (0.39–0.62) | 0.88 (0.79–0.94) | 4.22 (2.42–7.36) | 0.56 (0.45–0.69) | 2.02 (1.37–2.67) | 7.53 (3.92–14.47) | 0.73 (0.69–0.77) | ||
Storage method | ||||||||||
Cryopreservation | 1 | 0.51 | 0.51 | 1.06 | 0.95 | −c | 1.12 | – | < 0.001 | |
Fresh | 11 | 0.60 (0.41–0.76) | 0.87 (0.77–0.93) | 4.64 (3.04–7.08) | 0.46 (0.32–0.68) | 2.30 (1.80–2.80) | 9.99 (6.05–16.49) | 0.83 (0.80–0.86) | ||
Preparation method | ||||||||||
No preparation | 6 | 0.72 (0.50–0.87) | 0.80 (0.59–0.92) | 3.68 (1.90–7.13) | 0.35 (0.21–0.59) | 2.36 (1.71–3.01) | 10.56 (5.51–20.26) | 0.83 (0.79–0.86) | 0.006 | |
Swim up | 4b | 0.38 (0.24–0.54) | 0.86 (0.49–0.97) | 2.63 (0.75–9.18) | 0.73 (0.62–0.85) | 1.29 (− 0.06–2.63) | 3.62 (0.94–13.90) | 0.51 (0.47–0.56) | ||
Discontinuous gradient | 4 | 0.46 (0.28–0.65) | 0.90 (0.87–0.93) | 4.83 (2.64–8.83) | 0.60 (0.41–0.87) | 2.09 (1.14–3.04) | 8.08 (3.13–20.88) | 0.90 (0.87–0.92) | ||
FR cut-off value combined with AE assay method | ||||||||||
< 50% | Spectrophotometry | NC | ||||||||
Spectrophotometry/BAPNA | 4b | 0.63 (0.48–0.76) | 0.87 (0.60–0.97) | 4.96 (1.51–16.37) | 0.42 (0.32–0.57) | 2.46 (1.24–3.67) | 11.68 (3.47–39.36) | 0.75 (0.71–0.79) | ||
Substrate assay | ||||||||||
Acrosin target with gelatine substrate assay | 1 | 0.50 | 0.93 | 7.00 | 0.54 | – | 13.00 | 0.80d | ||
≤ 50% | Substrate assay | |||||||||
Acrosin target with gelatine substrate assay | 1 | 0.26 | 0.97 | 9.64 | 0.76 | – | 12.63 | – | ||
= 0% | Fluorometry | |||||||||
PAb-acrosin | 1 | 0.63 | 0.92 | 9.23 | 0.39 | – | 23.87 | – | ||
PAb-hyaluronidase | 1 | 0.23 | 0.90 | 2.29 | 0.86 | – | 2.68 | – | ||
MAb 4D4-proacrosin | 1 | 0.40 | 0.96 | 10.00 | 0.63 | – | 16.00 | 0.71d | ||
Spectrophotometry | ||||||||||
Spectrophotometry/BAPNA | 4 | 0.78 (0.38–0.95) | 0.63 (0.40–0.81) | 2.11 (1.25–3.55) | 0.35 (0.11–1.18) | 1.78 (0.29–3.27) | 5.94 (1.34–26.34) | 0.74 (0.70–0.78) | ||
Accu-sperm Spectrophotometry/BAPNA | 1 | 0.61 | 0.84 | 3.90 | 0.46 | – | 8.4 | – |
Spontaneous AR assay
Induced AR assay
Subgroup | N | Rs (95% CI) | Test(s) of heterogeneity | Significance test(s) of Rs = 0 |
P
a
| ||
---|---|---|---|---|---|---|---|
I2 (%) |
P
| Z |
P
| ||||
Overall | 17 | 0.40 (0.24–0.57) | 96.5 | 0.000 | 4.87 | 0.000 | |
Three experiments excluded | 14 | 0.36 (0.24–0.47) | 83.6 | 0.000 | 5.99 | 0.000 | |
Geographic area | |||||||
Europe | 10 | 0.33 (0.11–0.55) | 95.7 | 0.000 | 2.98 | 0.003 | < 0.001 |
Oceania | 2 | 0.40 (0.03–0.76) | 89.0 | 0.003 | 2.11 | 0.035 | |
South America | 1 | 0.46 (0.17–0.75) | –b | – | 3.14 | 0.002 | |
Africa | 2 | 0.65 (0.05–1.25) | 97.1 | 0.000 | 2.12 | 0.034 | |
North America | 2 | 0.49 (0.30–0.69) | 57.8 | 0.124 | 4.95 | 0.000 | |
Preparation method | |||||||
No preparation | 1 | 0.39 (0.20–0.58) | – | – | 4.12 | 0.000 | < 0.001 |
One preparation | 15 | 0.41 (0.24–0.58) | 96.7 | 0.000 | 4.63 | 0.000 | |
Swim up | 6 | 0.65 (0.49–0.81) | 93.0 | 0.000 | 8.07 | 0.000 | < 0.001 |
Swim up/discontinuous gradient | 2 | 0.61 (0.42–0.81) | 50.9 | 0.153 | 6.07 | 0.000 | |
Discontinuous gradient | 7 | 0.17 (0.10–0.25) | 19.0 | 0.285 | 4.42 | 0.000 | |
Double preparation | 1 | 0.33 (0.13–0.53) | – | – | 3.28 | 0.001 | |
AR trigger | |||||||
Physiological trigger | 8 | 0.49 (0.28–0.70) | 96.8 | 0.000 | 4.51 | 0.000 | < 0.001 |
HFF | 3 | 0.46 (−0.03–0.95) | 97.3 | 0.000 | 1.85 | 0.065 | < 0.001 |
P | 2 | 0.31(−0.01–0.63) | 82.4 | 0.017 | 1.89 | 0.059 | |
ZP | 3 | 0.63 (0.25–1.01) | 96.0 | 0.000 | 3.22 | 0.001 | |
Nonphysiological trigger | 9 | 0.33 (0.15–0.50) | 89.0 | 0.000 | 3.68 | 0.000 | |
A23187 | 5 | 0.36 (0.13–0.58) | 89.1 | 0.000 | 3.12 | 0.002 | < 0.001 |
CAMP | 1 | 0.12(−0.06–0.29) | – | – | 1.26 | 0.206 | |
TPA | 1 | 0.03 (−0.15–0.21) | – | – | 0.29 | 0.773 | |
BSA-GlcNAc/A23187 | 1 | 0.46 (0.17–0.75) | – | – | 3.14 | 0.002 | |
Mannose | 1 | 0.59 (0.42–0.76) | – | – | 6.68 | 0.000 | |
AR assay method | |||||||
Fluorescent labels | 16 | 0.41 (0.25–0.58) | 96.5 | 0.000 | 4.89 | 0.000 | < 0.001 |
Direct immunofluorescence | 15 | 0.40 (0.21–0.58) | 96.7 | 0.000 | 4.22 | 0.000 | 0.224 |
With lection | 10 | 0.53 (0.36–0.70) | 94.9 | 0.000 | 6.08 | 0.000 | < 0.001 |
FITC-PSA | 7 | 0.55 (0.36–0.75) | 95.7 | 0.000 | 5.57 | 0.000 | < 0.001 |
FITC-PNA | 2 | 0.40 (0.23–0.58) | 18.3 | 0.269 | 4.51 | 0.000 | |
RITC-PSA | 1 | 0.59 (0.42–0.76) | – | – | 6.68 | 0.000 | |
With antibody | |||||||
FITC-GB24 | 5 | 0.15 (0.05–0.25) | 40.3 | 0.152 | 2.93 | 0.003 | |
Indirect immunofluorescence | |||||||
Anti-CD46 antibody | 1 | 0.68 (0.59–0.77) | – | – | 14.14 | 0.000 | |
Triple stain | 1 | 0.24 (0.03–0.45) | – | – | 2.24 | 0.025 |
Subgroup | N | SMD (95% CI) | Test(s) of heterogeneity | Significance test(s) of SMD = 0 |
P
a
| ||
---|---|---|---|---|---|---|---|
I2 (%) |
P
| Z |
P
| ||||
Overall | 22 | 0.86 (0.60–1.11) | 78.7 | 0.000 | 6.55 | 0.000 | |
Four experiments excluded | 18 | 0.71 (0.52–0.90) | 54.8 | 0.003 | 7.25 | 0.000 | |
Geographic area | |||||||
Europe | 15 | 0.76 (0.44–1.07) | 82.1 | 0.000 | 4.68 | 0.000 | 0.001 |
Oceania | 1 | 0.66 (0.24–1.08) | –b | – | 3.10 | 0.002 | |
South America | 1 | 0.97 (0.15–1.78) | – | – | 2.33 | 0.020 | |
Africa | 1 | 1.86 (0.91–2.80) | – | – | 4.46 | 0.000 | |
North America | 1 | 1.91 (1.18–2.63) | – | – | 5.14 | 0.000 | |
Asia | 3 | 0.86 (0.48–1.24) | 0.0 | 0.589 | 4.46 | 0.000 | |
Preparation method | |||||||
No preparation | 0 | ||||||
One preparation | 22 | ||||||
Swim up | 8 | 1.51 (1.13–1.89) | 61.3 | 0.012 | 7.75 | 0.000 | < 0.001 |
Swim up/discontinuous gradient | 1 | 0.97 (0.15–1.78) | – | – | 4.79 | 0.000 | |
Discontinuous gradient | 13 | 0.47 (0.28–0.66) | 48.2 | 0.027 | 2.33 | 0.020 | |
Double preparation | 0 | ||||||
AR trigger | |||||||
Physiological trigger | 7 | 0.95 (0.29–1.61) | 89.1 | 0.000 | 2.81 | 0.005 | 0.92 |
HFF | 3 | 0.97 (−0.42–2.37) | 95.1 | 0.000 | 1.37 | 0.172 | 0.029 |
P | 3 | 0.65 (0.01–1.28) | 73.4 | 0.023 | 1.99 | 0.047 | |
ZP | 1 | 1.86 (0.91–2.80) | – | – | 3.85 | 0.000 | |
Nonphysiological trigger | 15 | 0.81 (0.56–1.06) | 67.6 | 0.000 | 6.36 | 0.000 | |
A23187 | 10 | 0.87 (0.66–1.08) | 26.1 | 0.204 | 8.30 | 0.000 | < 0.001 |
CAMP | 1 | −0.12 (−0.56–0.32) | – | – | 0.54 | 0.588 | |
TPA | 2 | 0.40 (0.09–0.70) | 0.0 | 0.866 | 2.54 | 0.011 | |
BSA-GlcNAc/A23187 | 1 | 0.97 (0.15–1.78) | – | – | 2.33 | 0.020 | |
Mannose | 1 | 1.91 (1.18–2.63) | – | – | 5.14 | 0.000 | |
AR assay method | |||||||
Fluorescent labels | 21 | 0.82 (0.57–1.08) | 78.3 | 0.000 | 6.26 | 0.000 | 0.012 |
Direct immunofluorescence | 19 | 0.80 (0.52–1.07) | 79.4 | 0.000 | 5.72 | 0.000 | 0.16 |
With lection | 12 | 1.16 (0.84–1.47) | 66.3 | 0.001 | 7.17 | 0.000 | < 0.001 |
FITC-PSA | 7 | 1.19 (0.68–1.71) | 77.5 | 0.000 | 4.53 | 0.000 | 0.060 |
FITC-PNA | 4 | 0.96 (0.66–1.25) | 0.0 | 0.961 | 6.27 | 0.000 | |
RITC-PSA | 1 | 1.91 (1.18–2.63) | – | – | 7.17 | 0.000 | |
With antibody | 7 | 0.28 (0.06–0.50) | 44.2 | 0.097 | 2.45 | 0.014 | |
FITC-GB24 | |||||||
Indirect immunofluorescence | 2 | 1.11 (0.26–1.95) | 64.2 | 0.094 | 2.57 | 0.010 | |
GB24 antibody | |||||||
Triple stain | 1 | 1.52 (0.87–2.18) | 78.7 | 0.000 | 4.57 | 0.000 |
Subgroup | N | SEN (95% CI) | SPE (95% CI) | PLR (95% CI) | NLR (95% CI) | DS (95% CI) | DOR (95% CI) | AUC (95% CI) |
P
a
|
---|---|---|---|---|---|---|---|---|---|
Overall | 13 | 0.79 (0.71–0.85) | 0.87 (0.74–0.94) | 6.08 (2.77–13.36) | 0.24 (0.17–0.35) | 3.22 (2.19–4.24) | 24.91 (8.91–69.66) | 0.84 (0.81–0.87) | |
Geographic area | |||||||||
Europe | 5 | 0.80 (0.66–0.89) | 0.86 (0.56–0.97) | 5.80 (1.46–23.10) | 0.23 (0.13–0.43) | 3.21 (1.51–4.91) | 24.81 (4.53–135.75) | 0.86 (0.83–0.89) | NC |
Oceania | 4b | 0.75 (0.59–0.86) | 0.77 (0.61–0.87) | 3.22 (1.70–6.08) | 0.33 (0.18–0.61) | 2.28 (1.11–3.45) | 9.78 (3.04–31.47) | 0.80 (0.77–0.84) | |
South America | 1 | 0.78 | 0.91 | 8.56 | 0.24 | −c | 35.00 | – | |
Africa | 4b | 0.94 (0.44–1.00) | 0.98 (0.85–1.00) | 52.54 (5.96–462.88) | 0.06 (0.00–1.00) | 6.76 (3.74–9.77) | 861.19 (42.25–17,552.00) | 0.99 (0.98–1.00) | |
North America | 4b | 0.77 (0.69–0.84) | 0.87 (0.64–0.96) | 6.11 (1.79–20.94) | 0.26 (0.16–0.41) | 3.17 (1.54–4.79) | 23.70 (4.68–120.00) | 0.83 (0.79–0.86) | |
Asia | 1 | 0.82 | 0.70 | 2.77 | 0.26 | – | 10.75 | – | |
Preparation method | |||||||||
No preparation | 1 | 0.71 | 0.55 | 1.58 | 0.53 | – | 3.00 | – | NC |
One preparation | 11 | 0.82 (0.73–0.88) | 0.87 (0.73–0.94) | 6.10 (2.84–13.09) | 0.21 (0.14–0.33) | 3.36 (2.32–4.39) | 28.70 (10.21–80.65) | 0.88 (0.85–0.91) | |
Double preparation | 1 | 0.63 | 1.00 | – | 0.40 | – | – | – | |
AR trigger | |||||||||
Physiological trigger | 10b | 0.82 (0.73–0.88) | 0.88 (0.76–0.94) | 6.78 (3.10–14.83) | 0.20 (0.13–0.33) | 3.50 (2.35–4.65) | 32.26 (10.53–105.06) | 0.89 (0.86–0.91) | NC |
Nonphysiological trigger | 8 | 0.79 (0.70–0.85) | 0.86 (0.65–0.95) | 5.70 (1.98–16.39) | 0.25 (0.16–0.37) | 3.14 (1.82–4.46) | 23.10 (6.16–81.56) | 0.82 (0.78–0.85) | |
AR assay method | |||||||||
Fluorescent labels | 11 | 0.78 (0.71–0.84) | 0.90 (0.78–0.96) | 8.01 (3.24–19.82) | 0.24 (0.18–0.34) | 3.49 (2.35–4.64) | 32.83 (10.44–103.21) | 0.83 (0.80–0.86) | |
Direct immunofluorescence | 10 | 0.78 (0.70–0.85) | 0.86 (0.74–0.93) | 5.72 (2.81–11.63) | 0.25 (0.17–0.37) | 3.12 (2.11–4.14) | 22.76 (8.23–62.95) | 0.84 (0.81–0.87) | |
FITC−PSA | 7 | 0.81 (0.69–0.88) | 0.83 (0.66–0.93) | 4.80 (2.09–11.01) | 0.23 (0.13–0.41) | 3.02 (1.72–4.32) | 20.51 (5.60–75.15) | 0.87 (0.83–0.89) | |
FITC−PNA | 4b | 0.68 (0.58–0.76) | 0.85 (0.81–0.88) | 4.55 (3.42–6.05) | 0.38 (0.28–0.50) | 2.49 (1.98–3.01) | 12.10 (7.24–20.21) | 0.85 (0.81–0.87) | |
RITC−PSA | 1 | 0.83 | 0.98 | 38.33 | 0.17 | – | 225.00 | – | |
Indirect immunofluorescence | |||||||||
Anti−CD46 antibody | 1 | 0.83 | 1.00 | – | 0.18 | – | – | – | |
Triple stain | 4b | 0.93 (0.76–0.98) | 0.58 (0.52–0.64) | 2.23 (1.96–2.54) | 0.12 (0.03–0.43) | 2.92 (1.59–4.25) | 18.56 (4.91–70.16) | 0.68 (0.64–0.72) |